Biomaterial-associated infections account for over one million nosocomial infections per year, and their prevention is a critical component to successful regenerative medicine strategies. Bacterial infection of biomaterial implants frequently results in complete removal of the implant despite aggressive antibiotic therapy. Staphylococcus aureus and Pseudomonas aeruginosa are the most clinically relevant gram positive and gram negative pathogens associated with medical device failure. Bacteriophages are bacteria-specific viruses that have the ability to infect and lyse host bacteria. We have recently engineered a poly (ethylene glycol) (PEG)-based hydrogel system for controlled delivery of therapeutic proteins that facilitates bone repair in a murine radial segmental defect model. Contamination of these hydrogels with bacteria leads to complete inhibition of bone healing, persistence of bacteria, and bone resorption. The objective of this project is to engineer PEG- based hydrogels that are infection resistant. The central hypothesis is that delivery of bacteriophage using a PEG-hydrogel will reduce infection in a mouse model for bone repair. Aim 1: Engineer hydrogels for controlled delivery of active bacteriophage to eliminate bacteria. Aim 2: Examine the ability of phage presenting hydrogels to reduce infection and improve bone repair. Aim 3: Characterize the in vivo inflammatory response to bacteriophage containing hydrogels. The proposed research is innovative because it focuses on developing biomaterials that resistant infection without the use of antibiotics, thereby reducing the development of antibiotic resistant bacteria while minimizing implanted device failure. As outcomes of this research, we will establish the feasibility of controlled bacteriophage release hydrogels to reduce infection and promote bone repair. This research will establish a strategy for infection-resistant biomaterials that is applicable to various biomedical devices.